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BackgroundDespite inadequate supply and potential contamination risk, human plasma has remained the only source for human serum albumin (pHSA) intravenous administration since the 1940s.ObjectiveWe sought to establish the safety and efficacy of OsrHSA, a recombinant HSA from bioengineered Oryza sativa (rice).DesignIn this multicentre, randomised, double-blind and positive-controlled study, patients with decompensated liver cirrhosis and serum albumin ≤30 g/L were recruited from 22 centres in China. The patients were randomly assigned to OsrHSA or pHSA (4:1) to once-daily intravenous injection (10 g or 20 g) until their serum albumin level reached 35 g/L, for a maximum of 2 weeks, with 2 weeks of follow-up. The primary outcome was the proportion of patients to reach a serum albumin level of 35 g/L (non-inferiority margin <−0.20). Outcomes were evaluated in patients who received the study drug and had at least one post-baseline serum albumin value (full analysis set, FAS). Safety was evaluated in all patients who received the study drug.ResultsBetween 22 March 2021 and 2 June 2022, 220 patients received OsrHSA (n=175) or pHSA (n=45). 216 patients were included in the FAS (OsrHSA, n=171; pHSA, n=45). Primary outcome of OsrHSA (130/171, 76%) was non-inferior to pHSA (34/45, 75.6%) (difference=0.5%; lower limit of 97.5% CI=−0.119). There was no significant difference between all secondary outcomes of OsrHSA and pHSA. There were no drug-related serious adverse events.ConclusionsRice-derived HSA is non-inferior to plasma-derived HSA in efficacy and safety. This finding should be confirmed in phase 3 trial.Trial registration number NCT04835480.

Cell surface glycans form various “glycan patterns” consisting of different types of glycan molecules, thus enabling strong and selective cell-to-cell recognition. We previously conjugated different N -glycans to human serum albumin to construct glycoalbumins mimicking natural glycan patterns that could selectively recognize target cells or control excretion pathways in mice. Here, we develop an innovative glycoalbumin capable of undergoing transformation and remodeling of its glycan pattern in vivo, which induces its translocation from the initial target to a second one. Replacing α(2,3)-sialylated N -glycans on glycoalbumin with galactosylated glycans induces the translocation of the glycoalbumin from blood or tumors to the intestine in mice. Such “in vivo glycan pattern remodeling” strategy can be used as a drug delivery system to promote excretion of a drug or medical radionuclide from the tumor after treatment, thereby preventing prolonged exposure leading to adverse effects. Alternatively, this study provides a potential strategy for using a single glycoalbumin for the simultaneous treatment of multiple diseases in a patient. Cell surface glycans form glycan patterns consisting of different types of glycan molecules, thus enabling strong and selective cell-to-cell recognition. In this study, the authors report a method based on the manipulation of glycan patterns to translocate a glycosylated albumin from blood or tumor to intestine by remodeling the α(2,3)-sialylated glycan pattern into a galactosylated pattern on albumin via a bioorthogonal chemical reaction.

In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioural outcome. In a pilot clinical trial, albumin doses as high as 2 g/kg were safely tolerated. We aimed to assess whether albumin given within 5 h of the onset of acute ischaemic stroke increased the proportion of patients with a favourable outcome. We did a randomised, double-blind, parallel-group, phase 3, placebo-controlled trial between Feb 27, 2009, and Sept 10, 2012, at 69 sites in the USA, 13 sites in Canada, two sites in Finland, and five sites in Israel. Patients aged 18–83 years with ischaemic (ie, non-haemorrhagic) stroke with a baseline National Institutes of Health stroke scale (NIHSS) score of 6 or more who could be treated within 5 h of onset were randomly assigned (1:1), via a central web-based randomisation process with a biased coin minimisation approach, to receive 25% albumin (2 g [8 mL] per kg; maximum dose 750 mL) or the equivalent volume of isotonic saline. All study personnel and participants were masked to the identity of the study drug. The primary endpoint was favourable outcome, defined as either a modified Rankin scale score of 0 or 1, or an NIHSS score of 0 or 1, or both, at 90 days. Analysis was by intention to treat. Thrombolytic therapies were permitted. This trial is registered with ClinicalTrials.gov, number NCT00235495. 422 participants were randomly assigned to receive albumin and 419 to receive saline. On Sept 12, 2012, the trial was stopped early for futility (n=841). The primary outcome did not differ between patients in the albumin group and those in the saline group (186 [44%] vs 185 [44%]; risk ratio 0·96, 95% CI 0·84–1·10, adjusted for baseline NIHSS score and thrombolysis stratum). Mild-to-moderate pulmonary oedema was more common in patients given albumin than in those given saline (54 [13%] of 412 vs 5 [1%] of 412 patients); symptomatic intracranial haemorrhage within 24 h was also more common in patients in the albumin group than in the placebo group (17 [4%] of 415 vs 7 [2%] of 414 patients). Although the rate of favourable outcome in patients given albumin remained consistent at 44–45% over the course of the trial, the cumulative rate of favourable outcome in patients given saline rose steadily from 31% to 44%. Our findings show no clinical benefit of 25% albumin in patients with ischaemic stroke; however, they should not discourage further efforts to identify effective strategies to protect the ischaemic brain, especially because of preclinical literature showing convincing proof-of-principle for the possibility of this outcome. National Institute of Neurological Disorders and Stroke, US National Institutes of Health; and Baxter Healthcare Corporation.

In this study, temperature-responsive polymer-protein conjugate was synthesized using a “grafting from” concept by introducing a chain transfer agent (CTA) into bovine serum albumin (BSA). The BSA-CTA was used as a starting point for poly(N-isopropylacrylamide) (PNIPAAm) through reversible addition-fragmentation chain transfer polymerization. The research investigations suggest that the thermally responsive behavior of PNIPAAm was controlled by the monomer ratio to CTA, as well as the amount of CTA introduced to BSA. The study further synthesized the human serum albumin (HSA)-PNIPAAm conjugate, taking the advantage that HSA can specifically adsorb indoxyl sulfate (IS) as a uremic toxin. The HSA-PNIPAAm conjugate could capture IS and decreased the concentration by about 40% by thermal precipitation. It was also revealed that the protein activity was not impaired by the conjugation with PNIPAAm. The proposed strategy is promising in not only removal of uremic toxins but also enrichment of biomarkers for early diagnostic applications.

Natural musculoskeletal systems have been widely recognized as an advanced robotic model for designing robust yet flexible microbots. However, the development of artificial musculoskeletal systems at micro-nanoscale currently remains a big challenge, since it requires precise assembly of two or more materials of distinct properties into complex 3D micro/nanostructures. In this study, we report femtosecond laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive protein (bovine serum albumin, BSA) as the smart muscle. To realize the programmable integration of the two materials into a 3D configuration, a successive on-chip two-photon polymerization (TPP) strategy that enables structuring two photosensitive materials sequentially within a predesigned configuration was proposed. As a proof-of-concept, we demonstrate a pH-responsive spider microbot and a 3D smart micro-gripper that enables controllable grabbing and releasing. Our strategy provides a universal protocol for directly printing 3D microbots composed of multiple materials. Musculoskeletal systems are recognized as a model for designing robust yet flexible microbots but the development of artificial musculoskeletal systems at nanoscale currently remains challenging. Here the authors report a laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive proteins as the smart muscle.

Activates the pituitary gland, leading to increased secretion of growth hormone. This activation plays a crucial role in growth, metabolism, and tissue repair. Bovine serum albumin, a well-studied protein, demonstrates the interaction between proteins-ligands and transports various compounds in the bloodstream. This study elucidates the molecular interactions between L-ornithine and BSA through spectroscopic analysis, identifying binding modes, constants, and structural changes. Molecular docking techniques are employed to correlate with experimental data from fluorescence and UV spectroscopy analyses.The study uses Fourier transform infrared spectroscopy, UV–Visible spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy and molecular docking to analyze the interaction between bovine serum albumin and L-ornithine, providing thermodynamic parameters for understanding the protein structure and its binding.The interactions between L-ornithine and bovine serum albumin (BSA) were characterized using UV–visible spectroscopy, which demonstrated a hyperchromic shift. Fluorescence spectroscopy revealed that L-ornithine quenches the intrinsic fluorescence of both BSA and human serum albumin (HSA) via a static quenching mechanism, resulting in the formation of stable BSA-L-ornithine and HSA-L-ornithine complexes. Furthermore, Fourier-transform infrared (FTIR) and circular dichroism (CD) spectroscopy indicated a decrease in the secondary structure of the proteins, as evidenced by shifts in the amide II band and a concomitant reduction in α-helix content. Molecular docking studies suggested that L-ornithine binds to BSA within subdomain II. Collectively, these findings provide valuable insights into the metabolic pathways of L-ornithine and its potential pharmacological relevance. The study involves more precise information which revealing the insight of L-ornithine bioavailability. The finding enhances our understanding of interaction with potential implications for drug delivery.

Gold nanoparticles (AuNPs) are potentially applicable in drug/nucleic acid delivery systems. Low toxicity, high stability, and bioavailability are crucial for the therapeutic use of AuNPs and they are mainly determined by their interactions with proteins and lipids on their route to the target cells. In this work, we investigated the interaction of two pegylated gold nanoparticles, AuNP14a and AuNP14b, with human serum proteins albumin (HSA) and transferrin (Tf) as well as dimyristoyl-phosphatidylcholine (DMPC) liposomes, which can be a representative of biomembranes. We showed that AuNP14a/b interacted with HSA and Tf changing their electrical, thermodynamic, and structural properties as evidenced by dynamic light scattering, zeta potential, transmission electron microscopy, circular dichroism, fluorescence quenching, and isothermal titration calorimetry. These nanoparticles penetrated the DMPC membrane suggesting their ability to reach a target inside the cell. In most of the effects, AuNP14b was more effective than AuNP14a, which might result from its more positive charge. Further studies are needed to evaluate whether the interaction of AuNP14a/b with HSA and Tf is safe for the cell/organism and whether they may safely penetrate natural membranes.

Quantifying glycated albumin (GA) levels in the blood is crucial for diagnosing diabetes because they strongly correlate with blood glucose concentration. In this study, a biotic/abiotic sandwich assay was developed for the facile, rapid, and susceptible detection of human serum albumin (HSA) and GA. The proposed sandwich detection system was assembled using a combination of two synthetic polymer receptors and natural antibodies. Molecularly imprinted polymer nanogels (MIP-NGs) for HSA (HSA-MIP-NGs) were used to mimic capture antibodies, whereas antibodies for HSA or GA were used as primary antibodies and fluorescent signaling MIP-NGs for the Fc domain of IgG (F-Fc-MIP-NGs) were used as a secondary antibody mimic to indicate the binding events. The HSA/anti-HSA/F-Fc-MIP-NGs complex, formed by incubating HSA and anti-HSA antibodies with F-Fc-MIP-NGs, was captured by HSA-MIP-NGs immobilized on the chips for fluorescence measurements. The analysis time was less than 30 min, and the limit of detection was 15 pM. After changing the anti-HSA to anti-GA (monoclonal antibody), the fluorescence response toward GA exceeded that of HSA, indicating successful GA detection using the proposed sandwich detection system. Therefore, the proposed system could change the detection property by changing a primary antibody, indicating that this system can be applied to various target proteins and, especially, be a powerful approach for facile and rapid analysis methods for proteins with structural similarity.

Biological macromolecules can condense into liquid domains. In cells, these condensates form membraneless organelles that can organize chemical reactions. However, little is known about the physical consequences of chemical activity in and around condensates. Working with model bovine serum albumin (BSA) condensates, we show that droplets swim along chemical gradients. Active BSA droplets loaded with urease swim toward each other. Passive BSA droplets show diverse responses to externally applied gradients of the enzyme’s substrate and products. In all these cases, droplets swim toward solvent conditions that favor their dissolution. We call this behavior “dialytaxis”, and expect it to be generic, as conditions which favor dissolution typically reduce interfacial tension, whose gradients are well-known to drive droplet motion through the Marangoni effect. These results could potentially suggest alternative physical mechanisms for active transport in living cells, and may enable the design of fluid micro-robots. Here the authors identify a generic coupling in phase-separated liquids between motility and phase equilibria perturbations: phase-separated droplets swim to their dissolution. This suggests alternative transport mechanism for biomolecular condensates.

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSAGLC, gHSAFRC) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicated that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSAGLC and gHSAFRC, compared to HSA, resulting in less stable drug–protein complexes. The study revealed that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand–albumin) and ternary systems (ligand–albumin–ligandconst) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS–albumin complex or LOS in the GLP–albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs, to ensure optimal therapeutic efficacy and safety.